Prior to the present invention, a variety of adjuvants have been reported in the literature to potentiate the immune response to numerous antigens and particularly, the immune response to vaccines. It is known that the Freund complete or incomplete adjuvants are considered the classic adjuvants to which most other adjuvants are compared. However, their reactogenicity precludes the clinical use of such adjuvants in animals or humans. Other materials, such as mineral oil and aluminum hydroxide, have also been used as adjuvants, but they invariably suffer from disadvantages. For example, oil is known to produce tissue irritation, and aluminum hydroxide may enhance antibody responses only minimally. Moreover, many of the adjuvants currently available contain components which are not metabolizable in humans, and accordingly, this greatly limits their use. Additionally, most adjuvants in use today, are difficult to prepare in that they may require time consuming procedures and the use, in some cases, of elaborate and expensive equipment to formulate a vaccine and adjuvant system.
More recently, as reported by Reynolds et al. in Infection and Immunity, Volume 28, No. 3, pages 937-943, 1980, some adjuvant activity of a metabolizable lipid emulsion was found with inactivated viral vaccines. It is indicated in this study that this lipid emulsion adjuvant significantly enhances the immune responses of several warm blooded species to inactivated viral antigens. It is also indicated that this lipid emulsion, which is comprised of highly refined peanut oil emulsified in aqueous vaccines with glycerol and lecithin, has advantages over other oil-based adjuvants. For example, the lipid components of the emulsion are metabolizable by normal host constituents if employed in humans or animals, are easily emulsified by gentle agitation, and are relatively non-reactogenic.
In the American Journal of Veterinary Research, Volume 44, No. 1, pages 72-75, 1983, a comparison of inactivated viral vaccines containing different emulsion adjuvants is set forth. It is indicated in this article that the immunization studies revealed marked differences in the effectiveness of mineral oil adjuvants and the lipid emulsion adjuvant as described in the Reynolds et al. reference.
However, while the literature discloses the use of a metabolizable lipid emulsion as an adjuvant, prior to the present invention, there has been no indication of the use of a metabolizable lipid emulsion with other components which would further potentiate an immune response.